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At least 1,081 records · Page 60Linked to original sources
PubMed1996

Transcription-mediated binding of peptide nucleic acid (PNA) to double-stranded DNA: sequence-specific suicide transcription.

Peptide nucleic acid (PNA) forms sequence-specific (PNA)2/DNA triplexes with one strand of double-stranded DNA by strand invasion. When formed with the template strand of DNA such a (PNA)2/DNA triplex can arrest transcription elongation in vitro and can thus act as an anti-gene agent. One of the major obstacles to applying PNA as an anti-gene agent in vivo is that PNA strand invasion occurs at a very slow rate under moderate salt conditions. In the present study we show that transcription can increase the rate of sequence-specific PNA binding dramatically. Such transcription-mediated PNA binding occurs three times as efficiently when the PNA target is situated on the non- template strand as compared with the template strand. Since transcription can mediate template strand-associated (PNA)2/DNA complexes which arrest further elongation, the action of RNA polymerase results in repression of its own activity, i.e. suicide transcription. These findings are highly relevant for the possible future use of PNA as an anti-gene agent.

Base Sequence↗
PubMed2001

Transcriptional adaptor and histone acetyltransferase proteins in Arabidopsis and their interactions with CBF1, a transcriptional activator involved in cold-regulated gene expression.

The ARABIDOPSIS CBF transcriptional activators bind to the CRT/DRE regulatory element present in the promoters of many cold-regulated genes and stimulate their transcription. Expression of the CBF1 proteins in yeast activates reporter genes carrying a minimal promoter with the CRT/DRE as an upstream regulatory element. Here we report that this ability of CBF1 is dependent upon the activities of three key components of the yeast Ada and SAGA complexes, namely the histone acetyltransferase (HAT) Gcn5 and the transcriptional adaptor proteins Ada2 and Ada3. This result suggested that CBF1 might function through the action of similar complexes in ARABIDOPSIS In support of this hypothesis we found that ARABIDOPSIS has a homolog of the GCN5 gene and two homologs of ADA2, the first report of multiple ADA2 genes in an organism. The ARABIDOPSIS GCN5 protein has intrinsic HAT activity and can physically interact in vitro with both the ARABIDOPSIS ADA2a and ADA2b proteins. In addition, the CBF1 transcriptional activator can interact with the ARABIDOPSIS GCN5 and ADA2 proteins. We conclude that ARABIDOPSIS encodes HAT-containing adaptor complexes that are related to the Ada and SAGA complexes of yeast and propose that the CBF1 transcriptional activator functions through the action of one or more of these complexes.

Acetyltransferases↗
PubMed1977

The sv40 transcription complex. II. Non-dissociation of protein from SV40 chromatin during transcription.

A small fraction of the SV40 chromatin isolated from infected monkey cell cultures by the Triton method contains active RNA polymerase which had initiated transcription in vivo. This viral transcription complex (VTC) was utilized to answer the question of whether proteins dissociate from chromatin during transcription in vitro. 3H-RNA was synthesized by the VTC under conditions such that over half the label was in transcripts which were longer than half the length of the SV40 genome. Virtually all of the 3H-RNA remained associated with the SV40 chromatin, causing an increase in sedimentation rate from 55S to 78S. The density of the VTC-3H-RNA complex indicated that less than 5% of the original protein dissociated from the SV40 DNA which served as a template for transcription. We conclude that SV40 chromatin can be transcribed while the proteins remain associated with the DNA.

Cell Line↗
PubMed2003

Transcript identification by analysis of short sequence tags--influence of tag length, restriction site and transcript database.

There exist a number of gene expression profiling techniques that utilize restriction enzymes for generation of short expressed sequence tags. We have studied how the choice of restriction enzyme influences various characteristics of tags generated in an experiment. We have also investigated various aspects of in silico transcript identification that these profiling methods rely on. First, analysis of 14 248 mRNA sequences derived from the RefSeq transcript database showed that 1-30% of the sequences lack a given restriction enzyme recognition site. Moreover, 1-5% of the transcripts have recognition sites located less than 10 bases from the poly(A) tail. The uniqueness of 10 bp tags lies in the range 90-95%, which increases only slightly with longer tags, due to the existence of closely related transcripts. Furthermore, 3-30% of upstream 10 bp tags are identical to 3' tags, introducing a risk of misclassification if upstream tags are present in a sample. Second, we found that a sequence length of 16-17 bp, including the recognition site, is sufficient for unique transcript identification by BLAST based sequence alignment to the UniGene Human non-redundant database. Third, we constructed a tag-to-gene mapping for UniGene and compared it to an existing mapping database. The mappings agreed to 79-83%, where the selection of representative sequences in the UniGene clusters is the main cause of the disagreement. The results of this study may serve to improve the interpretation of sequence-based expression studies and the design of hybridization arrays, by identifying short tags that have a high reliability and separating them from tags that carry an inherent ambiguity in their capacity to discriminate between genes. To this end, supplementary information in the form of a web companion to this paper is located at http:// biobase.biotech.kth.se/tagseq.

Algorithms↗
PubMed1998

Detection of TLS/FUS-CHOP fusion transcripts in myxoid and round cell liposarcomas by nested reverse transcription-polymerase chain reaction using archival paraffin-embedded tissues.

The reciprocal translocation t(12;16)(q13;p11) has been shown to be highly characteristic of myxoid and round cell subtypes of liposarcoma, and the TLS/FUS-CHOP fusion gene that resulted from the translocation is expected to be a diagnostic molecular marker of these sarcomas. In this study, we conducted a nested reverse transcription-polymerase chain reaction (RT-PCR)-based assay to detect the TLS/FUS-CHOP fusion gene transcripts using archival formalin-fixed, paraffin-embedded tumor specimens. Of 18 paraffin-embedded specimens from 16 myxoid and round cell liposarcoma cases, the fusion transcripts could be identified in 16 (89%) specimens from 15 (94%) cases. A sequence analysis using the PCR products confirmed that the detected messages were derived from either type I or type II TLS/FUS-CHOP fusion gene, the latter of which was predominant (80%). The results were consistent in primary and recurrent lesions of the same patients and in paraffin-embedded and snap-frozen samples from the same tumors. In two negative specimens, transcripts of the beta-actin gene could not be detected by RT-PCR, and intact mRNA including the fusion messages might have been degraded. No fusion transcripts were detected in snap-frozen or paraffin-embedded material of other types of tumors with myxoid morphology (seven myxoid malignant fibrous histiocytomas and four lipomas with myxoid change). These results indicate that this molecular assay can be applied to formalin-fixed, paraffin-embedded tumor tissues as a diagnostic aid for these subtypes of liposarcoma.

Adolescent↗
PubMed1987

Transcriptional activation of the major immediate early transcription unit of human cytomegalovirus by heat-shock, arsenite and protein synthesis inhibitors.

In Rat-9G cells several copies of the major immediate early (IE) transcription unit (regions 1 and 2) of the human cytomegalovirus (HCMV) are stably integrated. The cells show a repressed phenotype for IE expression but can be induced by inhibition of protein synthesis. In this report we present evidence that the repressed phenotype is due to the absence of IE transcription and that heat-shock and sodium arsenite treatments each result in the transcriptional activation of the repressed IE transcription unit. Either treatment resulted in the induction of HCMV IE transcripts and IE nuclear antigen expression. An octameric DNA sequence present in three of the 18 bp IE enhancer elements (GGACTTTC) resembles the cellular heat-shock element core consensus sequence and may therefore be involved in the heat-shock response.

Animals↗
PubMed1989

The transcription termination region of the adenovirus 2 major late transcript contains multiple functional elements.

In order to understand the process of transcription termination by eukaryotic RNA polymerase II, the transcription termination region of the advenovirus 2 major late transcription unit was analysed in a transient transfection system. Previously, it had been demonstrated that the entire sequence from map units (m.u.) 97.1 to 100 of the adenovirus 2 genome terminates transcription when inserted into the 5' or 3' untranslated sequences of the chloramphenicol acetyltransferase gene. Using subclones and Bal 31 deletion mutants of the termination region, we have shown that the termination region consists of multiple elements each capable of inhibiting gene expression independently. A DNA sequence analysis reveals the presence of a highly repetitive A-rich sequence motif throughout the entire termination region. The data suggest that the A-rich motif may mediate the transcription termination process.

Adenoviruses, Human↗
PubMed1998

Interaction of a nascent RNA structure with RNA polymerase is required for hairpin-dependent transcriptional pausing but not for transcript release.

Nascent RNA structures may regulate RNA chain elongation either directly through interaction with RNA polymerase or indirectly by disrupting nascent RNA contacts with polymerase or DNA. To distinguish these mechanisms we tested whether the effects of the his leader pause RNA hairpin could be mimicked by pairing of antisense DNA or RNA oligonucleotides to the nascent transcript. The his pause hairpin inhibits nucleotide addition when it forms 11 nucleotides from the transcript 3' end. It also can terminate transcription when base changes extend its stem to </=8 nucleotides from the 3' end. All oligonucleotides that disrupted the pause hairpin reduced the dwell time of RNA polymerase at the pause site dramatically, even when they mimicked the 11-nucleotide 3'-proximal RNA spacing or created a suitably positioned RNA loop. Oligonucleotides that paired </=8 nucleotides from the pause RNA 3' end could trigger transcript release, but only when added to an already paused complex. These results argue that direct interaction of a nascent RNA hairpin with RNA polymerase delays escape from a pause, but that indirect effects of a hairpin may trigger transcript release from a paused complex. Resistance of the paused complex to pyrophosphorolysis and its reversal by antisense oligonucleotides further suggest that interaction of the pause hairpin with RNA polymerase disengages the RNA 3' end from the active site.

DNA-Directed RNA Polymerases↗
PubMed2006

CREB transcription factor modulates Bcl2 transcription in response to C5a in HL-60-derived neutrophils.

BACKGROUND: Complement fragment C5a and neutrophils have been implicated in the pathogenesis of renal disease and C5a has also been shown to delay apoptosis of human neutrophils via a transcription-independent pathway. However, transcription-dependent pathways have not been well described. The present study examined whether activation of HL-60-derived neutrophils by C5a modulates the transcription of two members of the Bcl2 family, Bax (pro-apoptotic) and Bcl2 (anti-apoptotic) molecules, and whether the cAMP-response element-binding protein (CREB) transcription factor mediates these effects through the phosphatidylinositol 3-kinase (PI3K)/Akt and extra-cellular signal-regulated kinase (ERK) signalling pathways. MATERIALS AND METHODS: The human promyelocytic leukaemia HL-60 cell line was differentiated into neutrophils using 1.25% DMSO. Differentiated cells were incubated with recombinant human C5a for 30-120 min with, or without, pretreatment with wortmannin or PD98059. The cells were lysed and quantified for gene-specific Bax and Bcl2 mRNA. In separate experiments, cells were incubated with C5a for 5-30 min with, or without, pretreatment with wortmannin, PD98059, or alkaline phosphatase. Cells were then lysed and immunoblotted using antihuman phospho-CREB (Ser133) antibody. Apoptosis was assessed by measuring active caspase-3 in differentiated HL-60 cells. RESULTS: C5a inhibited caspase-3 activation in HL-60-derived neutrophils (P=0.003). C5a significantly increased the expression of Bcl2 mRNA (P=0.028), which was time-dependent, peaking at 30 min, and was abrogated in the presence of either wortmannin or PD98059 (both P=0.028). The C5a had no impact on Bax mRNA expression. The Bax : Bcl2 mRNA ratio markedly decreased at 30 min (P=0.028). Time-dependent effect of C5a on CREB phosphorylation was demonstrable and rapid, peaking at 5 min, and was abrogated by either wortmannin or PD98059 (both P=0.028). Phosphorylation of CREB, but not of Akt and ERK, was inhibited by alkaline phosphatase (P=0.028). The effect of C5a on Bcl2 mRNA expression was abrogated by alkaline phosphatase (P=0.028). The Bax : Bcl2 mRNA ratio markedly increased in the presence of alkaline phosphatase (P=0.046). CONCLUSIONS: This study demonstrates that C5a induces Bcl2 mRNA transcription in HL-60-derived neutrophils, which is mediated in part by CREB through the convergence of the PI3K/Akt and ERK-signalling pathways.

Alkaline Phosphatase↗
PubMed1992

Analysis of the transcriptional activity of the hut promoter in Bacillus subtilis and identification of a cis-acting regulatory region associated with catabolite repression downstream from the site of transcription.

Levels of transcripts initiated at a hut promoter in Bacillus subtilis were analysed. The addition of histidine to the culture medium increased the level of the transcript sixfold. In the presence of histidine and glucose together, the level of the transcript was reduced to the level in the absence of induction. Furthermore, addition of a mixture of 16 amino acids to cultures of induced cells and of catabolite-repressed cells decreased levels of the transcript 16-fold and 2.6-fold, respectively. Thus, it appears that at least three regulatory mechanisms associated with induction, catabolite repression, and amino acid repression, control the transcriptional activity of the hut promoter. Expression of the hut promoter-lacZ fusions that contained various regions of the hutP gene and deletion analysis of the hutP region revealed a cis-acting sequence associated with catabolite repression that was located between positions +204 and +231 or around position +203.

Amino Acids↗
PubMed1987

Transcription termination and processing of transcripts from tRNA-related Xenopus satellite DNA sequences.

Nucleotide sequence homologies have been found between the transcriptional unit of a Xenopus laevis satellite DNA containing 1037-bp monomeric repeats and tRNA-coding genes. Since the tRNA-homologous region forms only part of the transcriptional unit, we have analyzed the size of transcripts being made after injection of cloned DNA into Xenopus oocyte nuclei. Incubation for 6 h mainly results in three RNA species comprising 130, 180 and 196 nucleotides, which originate at the same initiation site but terminate at different T stretches. Longer incubation reveals a complex pattern of smaller RNAs most likely resulting from 3'-end processing of primary transcripts. All these RNAs are related to tRNA, since they contain the tRNA-homologous region which is close to the 5' end of the transcription unit.

Animals↗
PubMed1990

Effects of ageing on transcriptional and post-transcriptional regulation of malic enzyme and glucose-6-phosphate dehydrogenase in rat liver.

We previously found an age-dependent impairment of induction of lipogenic enzymes in rat liver [Iritani et al. (1981) Biochim. Biophys. Acta 665, 636-639]. Further, we have found that after refeeding a fat-free diet to fasted rats, increases in transcriptional rate, mRNA concentration and enzyme induction of hepatic malic enzyme and glucose-6-phosphate dehydrogenase were always lower in 18-month-old rats than in 1.5-month-old rats. In the young rats, the transcriptional rates reached the maximum level in 4 h and the mRNA reached maximum levels in 16 h. The peaks tended to delay in the older rats. The half-lives of the mRNAs were not significantly longer in the old than in the young animals. The incorporation of [3H]leucine into the enzyme proteins was also decreased roughly in proportion to the enzyme induction. The mRNA concentrations in the liver polysomes were roughly proportional to the total mRNA. Thus, no effects of ageing on mRNA stability or on the translational activity of the enzymes could be found. It is suggested that the age-dependent decreases of malic enzyme and glucose-6-phosphate dehydrogenase induction can be mainly ascribed to the transcriptional steps. Moreover, the transcriptional rate, mRNA concentration and induction of malic enzyme were increased by triiodothyronine treatment at a similar rate in both the young and old rats, but the absolute increments were lower in the old animals. The triiodothyronine response to malic enzyme induction also appeared to be primarily decreased at the transcription level.

Aging↗
PubMed1991

Regulation of the expression of a secreted acidic protein rich in cysteine (SPARC) in human fibroblasts by transforming growth factor beta. Comparison of transcriptional and post-transcriptional control with fibronectin and type I collagen.

Transforming growth factor beta (TGF-beta) and secreted protein acidic rich cysteine (SPARC) have been associated with the rapid remodeling of connective tissues that occurs in wound healing and developmental processes. To study the temporal and mechanistic aspects of TGF-beta-regulated extracellular-protein gene expression in human fibroblasts, confluent cells were pulse labeled for 30 min with [35S]methionine at various times following the single addition of 1.0 ng/ml TGF-beta. After a 4-h chase period, specific radiolabeled media proteins were isolated by either immunoprecipitation or affinity chromatography and quantitated. Stimulation of SPARC synthesis was first apparent 5 h after addition of TGF-beta, reached a maximum (3.5-fold increase) at 24 h and persisted for at least 96 h. A similar temporal response to TGF-beta was observed for the extracellular matrix proteins collagen and fibronectin. In contrast, TGF-beta induced a strong (greater than sixfold increase at 9 h after addition of TGF-beta), but transient stimulation of the synthesis of endothelial-type plasminogen activator inhibitor. Northern blot analysis showed that SPARC mRNA levels were increased by TGF-beta in parallel with increase in SPARC synthesis; a maximum 3.9-fold increase in SPARC mRNA being reached at 24 h. Similarly, the levels of both collagen and fibronectin mRNA were increased by TGF-beta treatment. In each case the stimulation of mRNA was blocked by the presence of the translation inhibitor, cycloheximide. Stability of SPARC mRNA (half-life of approximately 50 h) was not significantly altered by TGF-beta. In contrast, the stability of collagen and fibronectin mRNA were both increased in the presence of TGF-beta; the increased stability being pronounced in less dense cells. In addition to effects on stability, transcription of the collagen and fibronectin genes was increased 7 h after TGF-beta addition, but returned to control levels by 24 h. However, transcription of the SPARC gene was unaffected by TGF-beta at both time points and, together with the stability data, indicates that TGF-beta regulates SPARC expression via a nuclear post-transcriptional mechanism. Differential regulation of gene expression by TGF-beta in a precise temporal pattern via transcriptional and post-transcriptional pathways may be an important aspect of the response of fibroblast cells in a wound environment.

Animals↗
PubMed1994

Alternative splice site selection in the human growth hormone gene transcript and synthesis of the 20 kDa isoform: role of higher order transcript structure.

Expression of the human growth hormone (hGH) gene in somatotrophs of the anterior pituitary gland results in the synthesis and secretion of a major 22 kDa and a minor 20 kDa GH isohormone. The expression of these two proteins reflects the alternative utilization of a major (B) and a minor (B') splice acceptor site in exon 3 of the hGH-N transcript. By comparing the structure and splicing patterns of the hGH-N gene transcript with that of the structurally related, placentally expressed, hGH-V gene transcript, which uses only the major (B) exon 3 splice acceptor, it has been possible to define the cis-acting elements in exon 3 that are critical for activation of the B' splice acceptor. The present paper demonstrates that, in addition to the importance of sequences in the immediate proximity of the two alternative splice acceptor sites, additional more remote sequences in the transcript also contribute to this alternative splice site selection. The data further suggest that these more distal sequences do not act individually, but interact so that the net level of alternative splicing in exon 3 is dictated by the overall higher order structure of the hGH-N transcript.

Alternative Splicing↗
PubMed2005

Transcriptional regulation of activating transcription factor 3 involves the early growth response-1 gene.

Previously, our laboratory identified activating transcription factor 3 (ATF3) as up-regulated by nonsteroidal anti-inflammatory drugs using microarray analysis of mRNA from human colorectal cancer cells treated with sulindac sulfide. ATF3 is a transcription factor involved in cell growth, apoptosis, and invasion and is induced by a variety of anticancer and dietary compounds. However, the regulation of ATF3 by anticancer agents is not known. The promoter of ATF3 contains several transcription factor binding sites. We identified three putative Egr-1 binding sites in the promoter of ATF3 and report for the first time that the molecular mechanism responsible for the transcriptional regulation of ATF3 by two divergent pharmaceutical compounds, sulindac sulfide and troglitazone, involved the early growth response gene-1 (Egr-1). For example, overexpression of Egr-1 protein induced ATF3 mRNA 3.5-fold and transcriptional activity of an ATF3 promoter construct more than 20-fold. ATF3 and Egr-1 mRNA and protein and ATF3 promoter activity were induced by these compounds, whereas induction of ATF3 by these compounds was blocked by Egr-1 small interfering RNA. Sulindac sulfide and troglitazone regulated ATF3 promoter activity, which was suppressed when the two Egr-1 sites were mutated. These compounds induced phosphorylation of extracellular signal-regulated kinase1/2 (Erk1/2), whereas a dominant-negative inhibitor of mitogen-activate protein kinase kinase (MEK) 1 blocked the induction of ATF3. The MEK1/2 inhibitor PD98059 (2'-amino-3'-methoxyflavone) blocked the induction of ATF3 and Egr-1 mRNA expression and ATF3 promoter activity by these compounds. Therefore, this is a novel first report demonstrating that the expression of ATF3 occurs via Egr-1 downstream of Erk1/2.

Activating Transcription Factor 3↗
PubMed2005

A natural CYP2B6 TATA box polymorphism (-82T--> C) leading to enhanced transcription and relocation of the transcriptional start site.

We investigated the impact of promoter polymorphisms on transcription of the human CYP2B6 gene. In total, 98 DNA samples from white persons from a previously characterized liver bank were sequenced throughout 2.3 kilobases of upstream sequence and haplotype structures were determined using additional coding sequence information. HepG2 cells and primary rat and human hepatocytes were transfected with luciferase reporter gene constructs driven by 2033 base pairs (bp) of the most frequent promoter variants. The novel haplotype *22 (-1848C--> A, -801G--> T, -750T--> C, and -82T--> C) showed 3- to 9-fold enhanced transcriptional activity in all transfected cells. Constructs containing single mutations surprisingly revealed -82T--> C, predicted to disrupt a putative TATA box, to be alone responsible for this effect. In silico analysis and electrophoretic mobility shift assay demonstrated conversion of the putative TATA box into a functional CCAAT/enhancer-binding protein binding site. Analysis of transcriptional start sites showed the mutant promoter to be transcribed from a start site located approximately 30 bp downstream of the wild-type start site, consistent with the use of a noncanonical TATA box at -55 bp. Median CYP2B6 mRNA expression and bupropion hydroxylase activity as a selective marker of CYP2B6 catalytic activity were approximately 2-fold higher in livers genotyped -82TC as in those genotyped -82TT (20.4 versus 9.8 arbitrary units, p = 0.007, and 201.8 versus 106.7 pmol/mg/min, p = 0.042, respectively). This promoter polymorphism thus contributes to CYP2B6 functional variability and represents a novel mechanism by which mutations can enhance transcription. Furthermore, a detailed interspecies comparison of CYP2B promoters and transcriptional start sites provided novel insights into evolutionary relationships.

Animals↗
PubMed2001

Quantification of bacterial transcripts during infection using competitive reverse transcription-PCR (RT-PCR) and LightCycler RT-PCR.

Bacteria have evolved sophisticated regulatory circuits to modulate their gene expression in response to disparate environments. In order to monitor bacterial gene expression and regulation in the host, methods for direct transcript analysis from clinical specimens are needed. For most bacterial infections, amplification of the mRNAs of interest is necessary due to the low numbers of cells present and the low levels of specific transcripts. Here we compare two methods of quantitative reverse transcription-PCR (RT-PCR)-competitive RT-PCR using a one-tube system followed by standard gel analysis and the real-time detection of PCR product formation by fluorescence resonance energy transfer technology using the LightCycler unit. We isolated Staphylococcus aureus RNA directly from clinical specimens obtained from cystic fibrosis patients with chronic S. aureus lung infection and from an animal model of foreign-body infection with no further cultivation of the bacteria. Competitive RT-PCR and LightCycler RT-PCR were tested for their ability to quantify the transcription of a constitutively expressed gyrase gene (gyr) and a highly regulated alpha-toxin gene (hla) of S. aureus. Reproducible results were obtained with both methods. A sensitivity of 10(4) (gyr) and 10(3) (hla) copies, respectively, was reached, which was sufficient for the quantification of transcripts during bacterial infection. Overall, the competitive RT-PCR is a robust technique which does not need special RNA purification. On the negative side, it is labor intensive and time consuming, thus limiting the numbers of samples which can be analyzed at a given time. LightCycler RT-PCR is very susceptible to even traces of inhibitors, but it allows high-throughput processing of samples.

Animals↗
PubMed1998

Pseudomonas aeruginosa lasR transcription correlates with the transcription of lasA, lasB, and toxA in chronic lung infections associated with cystic fibrosis.

The role of Pseudomonas aeruginosa quorum-sensing systems in the lung infections associated with cystic fibrosis (CF) has not been examined. The purpose of this study was to determine if genes regulated by the LasR-LasI quorum-sensing system were coordinately regulated by the P. aeruginosa populations during the lung infections associated with CF. We also wanted to ascertain if there was a relationship between the expression of lasR, a transcriptional regulator, and some P. aeruginosa virulence factors during these infections. We extracted RNAs from the bacterial populations of 131 sputa taken from 23 CF patients. These RNAs were blotted and hybridized with probes to P. aeruginosa lasA, lasB, and toxA. The hybridization signals from each probe were ranked, and the rankings were analyzed by a Spearman rank correlation to determine if there was an association between the population transcript accumulations for the three genes. The correlations between the transcript accumulation patterns of pairs of the genes suggested that lasA, lasB, and toxA might be coordinately regulated during CF lung infections. To determine if this coordinate regulation might be due to regulation by LasR, we probed RNAs, extracted from 84 sputa, with the lasR, lasA, lasB, toxA, and algD probes. Statistical analysis indicated that lasR transcript accumulation correlated to lasA, lasB, toxA, and algD transcript accumulations. These results indicated that lasR may at least partially regulate or be coordinately regulated with lasA, lasB, toxA, and algD during the lung infections associated with CF. These results also suggested that the LasR-LasI quorum-sensing system may control the expression of at least some virulence factors in the lungs of patients with CF.

ADP Ribose Transferases↗